Thrombotric occlusion remains the most serious complication associated with clinical small caliber grafts used in peripheral vascular surgery and aortocoronary bypass. Although is has been recognized that factors contributing to thrombus formation include both graft and hemodynamic variables, their relative importance has not been defined. Using a baboon arteriovenous shunt model and selected clinical grafts, we propose to measure quantitatively relative rates destruction, deposition, and embolization of labeled platelets and fibrinogen, and to assess the effectiveness of various antithrombotic strategies. Initially we will use gamma camera imaging to measure simultaneously the deposition of 111 In-labeled platelets and 131 I-fibrinogen onto clinical Dacron and expanded Teflon (Gore-Tex) vascular grafts (3-5 mm i.d.). Since this ex vivo system permits repeated studies in a single animal and a high degree of spatial resolution for thrombus detection, localized thrombus deposition within vascular grafts will be systematically measured at various flow rates with respect to the following variables: graft type, length, diameter, degree of stenosis, angle of bifurcation, and radius of curvature. Grafts will also be studied after surface modification by glow discharge polymerization and seeding with autologous endothelium. Acute and chronic alterations in the circulating platelet pool will be assessed by measurements of platelet ADP, ATP, and serotonin, and by platelet survival using 14 C-serotonin and 111 in. Subsequently we will test the hypothesis that the patency of occluded grafts can be restored both ex vivo and in vivo using thrombolytic agents (urokinase and tissue plasminogen activator), and can be subsequently maintained with appropriate anticoagulant-antiplatelet therapy. Variables to be studied include thrombus size, age, composition, and the method of infusion of thrombolytic agents (systemic vs. local). By imaging a filter embolus detection system in heparinized animals we will measure directly the size, frequency, and fate of arterial emboli generated during fibrinolytic therapy. These studies are therefore intended to define the operational limits of small caliber grafts, and to permit the selection of optimal therapeutic strategies.